AU2004270200A1 - Compounds containing matrix metalloproteinase substrates and methods of their use - Google Patents
Compounds containing matrix metalloproteinase substrates and methods of their use Download PDFInfo
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- AU2004270200A1 AU2004270200A1 AU2004270200A AU2004270200A AU2004270200A1 AU 2004270200 A1 AU2004270200 A1 AU 2004270200A1 AU 2004270200 A AU2004270200 A AU 2004270200A AU 2004270200 A AU2004270200 A AU 2004270200A AU 2004270200 A1 AU2004270200 A1 AU 2004270200A1
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- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 125000006000 trichloroethyl group Chemical group 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 229920001567 vinyl ester resin Polymers 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- VWQVUPCCIRVNHF-UHFFFAOYSA-N yttrium atom Chemical compound [Y] VWQVUPCCIRVNHF-UHFFFAOYSA-N 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/0495—Pretargeting
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/0002—General or multifunctional contrast agents, e.g. chelated agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Optics & Photonics (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Physics & Mathematics (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US49996003P | 2003-09-03 | 2003-09-03 | |
US49996603P | 2003-09-03 | 2003-09-03 | |
US60/499,966 | 2003-09-03 | ||
US60/499,960 | 2003-09-03 | ||
PCT/US2004/028660 WO2005023314A1 (en) | 2003-09-03 | 2004-09-02 | Compounds containing matrix metalloproteinase substrates and methods of their use |
Publications (1)
Publication Number | Publication Date |
---|---|
AU2004270200A1 true AU2004270200A1 (en) | 2005-03-17 |
Family
ID=34278690
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
AU2004270200A Abandoned AU2004270200A1 (en) | 2003-09-03 | 2004-09-02 | Compounds containing matrix metalloproteinase substrates and methods of their use |
Country Status (6)
Country | Link |
---|---|
US (1) | US20050106100A1 (ja) |
EP (1) | EP1691845A4 (ja) |
JP (1) | JP2007504242A (ja) |
AU (1) | AU2004270200A1 (ja) |
CA (1) | CA2537771A1 (ja) |
WO (1) | WO2005023314A1 (ja) |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1522857A1 (en) * | 2003-10-09 | 2005-04-13 | Universiteit Maastricht | Method for identifying a subject at risk of developing heart failure by determining the level of galectin-3 or thrombospondin-2 |
JP5368099B2 (ja) | 2005-10-07 | 2013-12-18 | ゲルベ | ガリウムと錯体形成することが可能なシグナル部分にカップリングされた、生物学的標的の認識のための部分を含んでなる化合物 |
US8986650B2 (en) | 2005-10-07 | 2015-03-24 | Guerbet | Complex folate-NOTA-Ga68 |
CA2644694C (en) * | 2006-03-10 | 2014-05-13 | Sangeeta N. Bhatia | Triggered self-assembly conjugates and nanosystems |
CA2648382C (en) | 2006-04-04 | 2016-10-11 | Singulex, Inc. | Methods and compositions for highly sensitive analysis of markers and detection of molecules |
US7838250B1 (en) | 2006-04-04 | 2010-11-23 | Singulex, Inc. | Highly sensitive system and methods for analysis of troponin |
GB0707034D0 (en) | 2007-04-12 | 2007-05-23 | St Andrews The | Compounds |
US20110165606A1 (en) * | 2007-06-15 | 2011-07-07 | Tutturen Astrid E V | Methods for modifying, isolating, detecting, visualizing, and quantifying citrullinated and/or homocitrullinated peptides, polypeptides and proteins |
EP3492488A1 (en) * | 2007-08-22 | 2019-06-05 | The Regents of The University of California | Activatable binding polypeptides and methods of identification and use thereof |
EP2198040B1 (en) * | 2007-08-31 | 2018-08-15 | Case Western Reserve University | In vivo imaging of myelin |
EP2240206B1 (en) * | 2008-01-08 | 2017-03-22 | Lantheus Medical Imaging, Inc. | N-alkoxyamide conjugates as imaging agents |
GB0819287D0 (en) | 2008-10-22 | 2008-11-26 | Univ Bradford | Compounds |
KR101678703B1 (ko) * | 2008-10-29 | 2016-11-23 | 비쥐 메디신, 인코포레이티드 | 갈렉틴-3 면역검정 |
JP5851842B2 (ja) | 2009-01-12 | 2016-02-03 | サイトムエックス セラピューティクス, インク.CytomX Therapeutics, Inc. | 改変した抗体組成物、それを作製および使用する方法 |
US8399219B2 (en) | 2009-02-23 | 2013-03-19 | Cytomx Therapeutics, Inc. | Protease activatable interferon alpha proprotein |
JP5678045B2 (ja) | 2009-06-08 | 2015-02-25 | シンギュレックス・インコーポレイテッド | 高感度バイオマーカーパネル |
JP5676600B2 (ja) | 2009-07-08 | 2015-02-25 | ランセウス メディカル イメージング, インコーポレイテッド | 造影剤としてのn−アルコキシアミド抱合体 |
BR112012008063A2 (pt) * | 2009-08-25 | 2016-11-22 | Bg Medicine Inc | galectina-3 e terapia de ressincronização cardíaca. |
EP2775906B1 (en) | 2011-11-11 | 2019-07-03 | Yale University | Evaluation of presence of and vulnerability to atrial fibrillation and other indications using matrix metalloproteinase-based imaging |
GB2516882A (en) | 2013-08-02 | 2015-02-11 | Univ Bradford | Tumour-targeted theranostic |
RU2607041C2 (ru) * | 2015-05-29 | 2017-01-10 | Общество с ограниченной ответственностью "Научно-производственная фирма ДНК-Технология" | Способ определения степени гноетечения на пародонте по уровню мРНК гена интерлейкина-8 (IL-8) человека |
EP3579821A1 (en) * | 2017-02-10 | 2019-12-18 | Boston Scientific Scimed, Inc. | Vascular ulcer treatment |
US11028123B2 (en) | 2018-04-10 | 2021-06-08 | Sanofi-Aventis Deutschland Gmbh | Capping of unprotected amino groups during peptide synthesis |
IN202021002695A (ja) * | 2020-01-21 | 2021-07-23 | ||
JP2023550412A (ja) * | 2020-11-19 | 2023-12-01 | ノバルティス アーゲー | 前立腺特異的膜抗原(psma)リガンドの合成 |
Family Cites Families (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4859777A (en) * | 1981-07-01 | 1989-08-22 | Eastman Kodak Company | Terpyridine chelating agents |
US4452774A (en) * | 1982-04-30 | 1984-06-05 | President And Fellows Of Harvard College | Isonitrile radionuclide complexes for labelling and imaging agents |
AU6621586A (en) * | 1985-11-18 | 1987-06-02 | University Of Texas System, The | Polychelating agents for image and spectral enhancement (and spectral shift) |
CA1305160C (en) * | 1985-12-23 | 1992-07-14 | Paul Louis Bergstein | Ether isonitriles and radiolabeled complexes thereof |
US4913891A (en) * | 1986-04-17 | 1990-04-03 | The United States Of America As Represented By The United States Department Of Energy | Positron emitter labeled enzyme inhibitors |
US5252317A (en) * | 1986-11-10 | 1993-10-12 | The State Of Oregon Acting By And Through The State Board Of Higher Education On Behalf Of The University Of Oregon | Amplifier molecules for diagnosis and therapy derived from 3,5-bis[1-(3-amino-2,2-bis (aminomethyl)-propyl) oxymethyl] benzoic acid |
US5567411A (en) * | 1986-11-10 | 1996-10-22 | State Of Oregon Acting By And Through The State Board Of Higher Education On Behalf Of The University Of Oregon | Dendritic amplifier molecules having multiple terminal active groups stemming from a benzyl core group |
US5064956A (en) * | 1987-06-24 | 1991-11-12 | The Dow Chemical Company | Process for preparing mono-n-alkylated polyazamacrocycles |
US5087440A (en) * | 1989-07-31 | 1992-02-11 | Salutar, Inc. | Heterocyclic derivatives of DTPA used for magnetic resonance imaging |
GB8923843D0 (en) * | 1989-10-23 | 1989-12-13 | Salutar Inc | Compounds |
GB9006977D0 (en) * | 1990-03-28 | 1990-05-23 | Nycomed As | Compositions |
US5482699A (en) * | 1991-03-27 | 1996-01-09 | Nycomed Salutar Inc. | Multinuclear complexes for x-ray imaging |
GB9209641D0 (en) * | 1992-05-02 | 1992-06-17 | Johnson Matthey Plc | Improvements in radiolabelling |
US5760191A (en) * | 1993-02-05 | 1998-06-02 | Nycomed Imaging As | Macrocyclic complexing agents and targeting immunoreagents useful in therapeutic and diagnostic compositions and methods |
US5750088A (en) * | 1993-03-30 | 1998-05-12 | The Dupont Merck Pharmaceutical Company | Stable hydrazones linked to a peptide moiety as reagents for the preparation of radiopharmaceuticals |
US5744120A (en) * | 1993-03-30 | 1998-04-28 | The Dupont Merick Pharmaceutical Company | Ternary radiopharmaceutical complexes |
MXPA94002323A (es) * | 1993-03-31 | 2002-06-18 | Mallinckrodt Medical Inc | Formulaciones radiofarmaceuticas que tienen reductores no estanosos. |
US5417959A (en) * | 1993-10-04 | 1995-05-23 | Mallinckrodt Medical, Inc. | Functionalized aza-crytand ligands for diagnostic imaging applications |
US5520904A (en) * | 1995-01-27 | 1996-05-28 | Mallinckrodt Medical, Inc. | Calcium/oxyanion-containing particles with a polymerical alkoxy coating for use in medical diagnostic imaging |
SE515621C2 (sv) * | 1995-05-08 | 2001-09-10 | Ericsson Telefon Ab L M | Förfarande vid lägesbestämning |
US5801228A (en) * | 1995-06-07 | 1998-09-01 | Nycomed Imaging As | Polymeric contrast agents for medical imaging |
IT1275571B (it) * | 1995-07-19 | 1997-08-07 | Consiglio Nazionale Ricerche | Substrati fluorogenici suscettibili di fotoattivazione previa trasformazione per via enzimatica atti alla diagnosi ed alla terapia fotodinamica dei tumori |
ES2217408T3 (es) * | 1996-04-01 | 2004-11-01 | Epix Medical, Inc. | Agentes diagnosticos de contraste para formacion de imagenes bioactivados. |
US5804161A (en) * | 1996-05-14 | 1998-09-08 | Nycomed Salutar Inc. | Contrast agents |
DE19717904A1 (de) * | 1997-04-23 | 1998-10-29 | Diagnostikforschung Inst | Säurelabile und enzymatisch spaltbare Farbstoffkonstrukte zur Diagnostik mit Nahinfrarotlicht und zur Therapie |
US6083486A (en) * | 1998-05-14 | 2000-07-04 | The General Hospital Corporation | Intramolecularly-quenched near infrared fluorescent probes |
US5980863A (en) * | 1998-11-02 | 1999-11-09 | Eagle Vision Pharmaceutical Corporation | Manganese compositions and methods for MRI |
US6254852B1 (en) * | 1999-07-16 | 2001-07-03 | Dupont Pharmaceuticals Company | Porous inorganic targeted ultrasound contrast agents |
US6656448B1 (en) * | 2000-02-15 | 2003-12-02 | Bristol-Myers Squibb Pharma Company | Matrix metalloproteinase inhibitors |
US20030004141A1 (en) * | 2001-03-08 | 2003-01-02 | Brown David L. | Medical devices, compositions and methods for treating vulnerable plaque |
-
2004
- 2004-09-01 US US10/931,627 patent/US20050106100A1/en not_active Abandoned
- 2004-09-02 WO PCT/US2004/028660 patent/WO2005023314A1/en active Application Filing
- 2004-09-02 JP JP2006525453A patent/JP2007504242A/ja active Pending
- 2004-09-02 CA CA002537771A patent/CA2537771A1/en not_active Abandoned
- 2004-09-02 AU AU2004270200A patent/AU2004270200A1/en not_active Abandoned
- 2004-09-02 EP EP04783037A patent/EP1691845A4/en not_active Withdrawn
Also Published As
Publication number | Publication date |
---|---|
EP1691845A1 (en) | 2006-08-23 |
US20050106100A1 (en) | 2005-05-19 |
JP2007504242A (ja) | 2007-03-01 |
CA2537771A1 (en) | 2005-03-17 |
EP1691845A4 (en) | 2009-02-25 |
WO2005023314A1 (en) | 2005-03-17 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
MK4 | Application lapsed section 142(2)(d) - no continuation fee paid for the application |